A Tripodal Ruthenium–Gadolinium Metallostar as a Potential α_vβ₃ Integrin Specific Bimodal Imaging Contrast Agent

Abstract

Gd^III-containing <i>metallostar</i> contrast agents are gaining increased attention, because their architecture allows for a slower tumbling rate, which, in turn, results in larger relaxivities. So far, these <i>metallostars</i> find possible applications as blood pool contrast agents. In this work, the first example of a tissue-selective <i>metallostar</i> contrast agent is described. This RGD-peptide decorated Ru^II(Gd^III)₃ <i>metallostar</i> is synthesized as an α_vβ₃-integrin specific contrast agent, with possible applications in the detection of atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a relaxivity of 9.65 s^–1 mM^–1, which represents an increase of 170%, compared to a low-molecular-weight analogue, because of a decreased tumbling rate (τ_R = 470 ps). The presence of the MLCT band (absorption 375–500 nm, emission 525–850 nm) of the central Ru^II(Ph-Phen)₃-based complex grants the <i>metallostar</i> attractive luminescent properties. The ³MLCT emission is characterized by a quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting candidate for time-gated luminescence imaging. The potential application as a selective MRI contrast agent for α_vβ₃-integrin expressing tissues is shown by an <i>in vitro</i> relaxometric analysis, as well as an <i>in vitro</i> <i>T</i>₁-weighted MR image